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Axonal myelin increase in the callosal genu in depression but not schizophrenia

Published online by Cambridge University Press:  25 February 2015

M. R. Williams ,
P. Sharma ,
K. L. Fung ,
R. K. B. Pearce ,
S. R. Hirsch  and
M. Maier
M. R. Williams*
Affiliation:
King's College London, Institute of Psychiatry, De Crespigny Park, London, UK Neuropathology Unit, Division of Experimental Medicine, Imperial College London, Charing Cross Campus, London, UK
P. Sharma
Affiliation:
Neuropathology Unit, Division of Experimental Medicine, Imperial College London, Charing Cross Campus, London, UK St George's University of London, London, UK
K. L. Fung
Affiliation:
Li Ka Shing Faculty of Medicine University of Hong Kong, Hong Kong
R. K. B. Pearce
Affiliation:
Neuropathology Unit, Division of Experimental Medicine, Imperial College London, Charing Cross Campus, London, UK
S. R. Hirsch
Affiliation:
Neuropathology Unit, Division of Experimental Medicine, Imperial College London, Charing Cross Campus, London, UK
M. Maier
Affiliation:
Trust HQ, West London Mental Health NHS Trust, Southall, Middlesex UK
*
* Address for correspondence: Dr M. R. Williams, Francis Fraser Clinic, Hammersmith Hospital, London W12 0NN, UK. (Email: Matthew.r.williams@imperial.ac.uk)
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Abstract

Background

Abnormalities in the anterior inter-hemispheric connectivity have previously been implicated in major depressive disorder. Disruptions in fractional anisotropy in the callosum and fornix have been reported in schizophrenia and major depressive disorder. Oligodendrocyte density and overall size of the callosum and fornix show no alteration in either illness, suggesting that gross morphology is unchanged but more subtle organizational disruption may exist within these brain regions in mood and affective disorders.

Method

Using high-resolution oil-immersion microscopy we examined the cross-sectional area of the nerve fibre and the axonal myelin sheath, and using standard high-resolution light microscopy we measured the density of myelinated axons. These measurements were made in the genu of the corpus callosum and the medial body of the fornix at its most dorsal point. Measures were taken in the sagittal plane in the callosal genu and in the coronal plane at the most dorsal part of the fornix body.

Results

Cases of major depressive disorder had significantly greater mean myelin cross-sectional area (p = 0.017) and myelin thickness (p = 0.004) per axon in the genu than in control or schizophrenia groups. There was no significant change in the density of myelinated axons, and no changes observed in the fornix.

Conclusion

The results suggest a clear increase of myelin in the axons of the callosal genu in MDD, although this type of neuropathological study is unable to clarify whether this is caused by changes during life or has a developmental origin.

Keywords

Axonscallosumdepressionneuropathology
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 10 , July 2015 , pp. 2145 - 2155
Copyright
Copyright © Cambridge University Press 2015 

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References

Abdul-Rahman, MF, Qiu, A, Sim, K (2011). Regionally specific white matter disruptions of fornix and cingulum in schizophrenia. PLoS ONE 14, e18652.Google Scholar
Aston, C, Jiang, L, Sokolov, BP (2004). Microarray analysis of postmortem temporal cortex from patients with schizophrenia. Journal of Neuroscience Research 77, 858–866.CrossRefGoogle ScholarPubMed
Aston, C, Jiang, L, Sokolov, BP (2005). Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder. Molecular Psychiatry 10, 309–322.CrossRefGoogle ScholarPubMed
Babcock, DS (1984). The normal, absent, and abnormal corpus callosum: sonographic findings. Radiology 151, 449–453.CrossRefGoogle ScholarPubMed
Barley, K, Dracheva, S, Byne, W (2009) Subcortical oligodendrocyte- and astrocyte-associated gene expression in subjects with schizophrenia, major depression and bipolar disorder. Schizophrenia Research 112, 54–64.CrossRefGoogle ScholarPubMed
Bernstein, HG, Klix, M, Dobrowolny, H, Brisch, R, Steiner, J, Bielau, H, Gos, T, Bogerts, B (2012). A postmortem assessment of mammillary body volume, neuronal number and densities, and fornix volume in subjects with mood disorders. European Archives of Psychiatry and Clinical Neuroscience 262, 637–646.CrossRefGoogle ScholarPubMed
Bigelow, LB, Rosenthal, R (1972). Schizophrenia and the corpus callosum. Lancet 7752, 694.CrossRefGoogle Scholar
Bigelow, LB, Nasrallah, HA, Rauscher, FP (1983). Corpus callosum thickness in chronic schizophrenia. British Journal of Psychiatry 142, 284–287.CrossRefGoogle ScholarPubMed
Bora, E, Fornito, A, Radua, J, Walterfang, M, Seal, M, Wood, SJ, Yücel, M, Velakoulis, D, Pantelis, C (2011). Neuroanatomical abnormalities in schizophrenia: a multimodal voxelwise meta-analysis and meta-regression analysis. Schizophrenia Research 127, 46–57.CrossRefGoogle ScholarPubMed
Bourne, VJ, Vladeanu, M (2013). Examining the relationship between lateralisation for processing emotional faces, depression, and sex. Laterality 18, 748–766.CrossRefGoogle ScholarPubMed
Bracht, T, Federspiel, A, Schnell, S, Horn, H, Höfle, O, Wiest, R, Dierks, T, Strik, W, Müller, TJ, Walther, S (2012). Cortico-cortical white matter motor pathway microstructure is related to psychomotor retardation in major depressive disorder. PLoS ONE 7, e52238.CrossRefGoogle ScholarPubMed
Brisch, R, Bernstein, HG, Stauch, R, Dobrowolny, H, Krell, D, Truebner, K, Meyer-Lotz, G, Bielau, H, Steiner, J, Kropf, S, Gos, T, Danos, P, Bogerts, B (2008). The volumes of the fornix in schizophrenia and affective disorders: a post-mortem study. Psychiatry Research 164, 265–273.CrossRefGoogle ScholarPubMed
Buchy, L, Luck, D, Czechowska, Y, Malla, A, Joober, R, Lepage, M (2012). Diffusion tensor imaging tractography of the fornix and belief confidence in first-episode psychosis. Schizophrenia Research 137, 80–84.CrossRefGoogle ScholarPubMed
Carrasco, JL, Tajima-Pozo, K, Díaz-Marsá, M, Casado, A, López-Ibor, JJ, Arrazola, J, Yus, M (2012). Microstructural white matter damage at orbitofrontal areas in borderline personality disorder. Journal of Affective Disorders 139, 149–153.CrossRefGoogle ScholarPubMed
Cotter, DR, Mackay, D, Beasley, CL, Everall, I and Landau, S (2002). The density, size and spatial pattern distribution of neurons and glia in area 9 prefrontal cortex in schizophrenia, bipolar disorder and major depression. Schizophrenia Research 3, 107–108.Google Scholar
Curčić-Blake, B, Nanetti, L, van der Meer, L, Cerliani, L, Renken, R, Pijnenborg, GH, Aleman, A (2013). Not on speaking terms: hallucinations and structural network disconnectivity in schizophrenia. Brain Structure and Function 220, 407–418.CrossRefGoogle ScholarPubMed
Davidson, CA, Kuroki, N, Alvarado, JL, Niznikiewicz, MA, McCarley, RW, Levitt, JJ (2012). An MRI study of septi pellucidi in relation to hippocampus volume and fornix integrity in schizophrenia. Schizophrenia Research 134, 165–170.CrossRefGoogle ScholarPubMed
Davis, KL, Stewart, DG, Friedman, JI, Buchsbaum, M, Harvey, PD, Hof, PR, Buxbaum, J, Haroutunian, V (2003). White matter changes in schizophrenia: evidence for myelin-related dysfunction. Archives of General Psychiatry 60, 443–456.CrossRefGoogle ScholarPubMed
Foong, J, Maier, M, Clark, CA, Barker, GJ, Miller, DH, Ron, MA (2000). Neuropathological abnormalities of the corpus callosum in schizophrenia: a diffusion tensor imaging study. Journal of Neurology, Neurosurgery & Psychiatry 68, 242–244.CrossRefGoogle ScholarPubMed
Gaiteri, C, Sibille, E (2011). Differentially expressed genes in major depression reside on the periphery of resilient gene coexpression networks. Frontiers of Neuroscience 5, 95.CrossRefGoogle ScholarPubMed
Griffiths, PD, Batty, R, Connolly, DA, Reeves, MJ (2009). Effects of failed commissuration on the septum pellucidum and fornix: implications for fetal imaging. Neuroradiology 51, 347–356.CrossRefGoogle ScholarPubMed
Guo, WB, Liu, F, Chen, JD, Xu, XJ, Wu, RR, Ma, CQ, Gao, K, Tan, CL, Sun, XL, Xiao, CQ, Chen, HF, Zhao, JP (2012). Altered white matter integrity of forebrain in treatment-resistant depression: a diffusion tensor imaging study with tract-based spatial statistics. Progress in Neuro-Psychopharmacology & Biological Psychiatry 38, 201–206.CrossRefGoogle ScholarPubMed
Hakak, Y, Walker, JR, Li, C, Wong, WH, Davis, KL, Buxbaum, JD, Haroutunian, V, Fienberg, AA (2001). Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proceedings of the National Academy of Sciences USA 98, 4746–4751.CrossRefGoogle ScholarPubMed
Haukvik, UK, Hartberg, CB, Agartz, I (2014). Schizophrenia – what does structural MRI show? Tidsskr Nor Laegeforen 133, 850–853.CrossRefGoogle Scholar
Heller, AS, Johnstone, T, Light, SN, Peterson, MJ, Kolden, GG, Kalin, NH, Davidson, RJ (2013). Relationships between changes in sustained fronto-striatal connectivity and positive affect in major depression resulting from antidepressant treatment. American Journal of Psychiatry 170, 197–206.CrossRefGoogle ScholarPubMed
Hof, PR, Haroutunian, V, Copland, C, Davis, KL, Buxbaum, JD (2002). Molecular and cellular evidence for an oligodendrocyte abnormality in schizophrenia. Neurochemical Research 27, 1193–1200.CrossRefGoogle ScholarPubMed
Hofer, S, Frahm, J (2006). Topography of the human corpus callosum revisited–comprehensive fiber tractography using diffusion tensor magnetic resonance imaging. Neuroimage 32, 989–994.CrossRefGoogle ScholarPubMed
Hoogenboom, WS, Perlis, RH, Smoller, JW, Zeng-Treitler, Q, Gainer, VS, Murphy, SN, Churchill, SE, Kohane, IS, Shenton, ME, Iosifescu, DV (2012). Limbic system white matter microstructure and long-term treatment outcome in major depressive disorder: a diffusion tensor imaging study using legacy data. World Journal of Biological Psychiatry 15, 122–134.CrossRefGoogle ScholarPubMed
Kandel, ER (2000). Nerve cells and behavior. In Principles of Neural Science 4th edn. (ed. Kandel, E.R., Schwartz, J.H. and Jessel, T.M.), pp. 19–35. McGraw Hill: New York.Google Scholar
Kasper, BS, Taylor, DC, Janz, D, Kasper, EM, Maier, M, Williams, MR, Crow, TJ (2010). Neuropathology of epilepsy and psychosis: the contributions of J.A.N. Corsellis. Brain 133, 3795–3805.CrossRefGoogle ScholarPubMed
Katsel, P, Davis, KL, Haroutunian, V (2005). Variations in myelin and oligodendrocyte-related gene expression across multiple brain regions in schizophrenia: a gene ontology study. Schizophrenia Research 79, 157–173.CrossRefGoogle ScholarPubMed
Kempton, MJ, Salvador, Z, Munafò, MR, Geddes, JR, Simmons, A, Frangou, S, Williams, SC (2011). Structural neuroimaging studies in major depressive disorder. Meta-analysis and comparison with bipolar disorder. Archives of General Psychiatry 68, 675–690.CrossRefGoogle ScholarPubMed
Keshavan, MS, Diwadkar, VA, Harenski, K, Rosenberg, DR, Sweeney, JA, Pettegrew, JW (2002). Abnormalities of the corpus callosum in first episode, treatment naive schizophrenia. Journal of Neurology, Neurosurgery and Psychiatry 72, 757–760.CrossRefGoogle ScholarPubMed
Kunimatsu, N, Aoki, S, Kunimatsu, A, Abe, O, Yamada, H, Masutani, Y, Kasai, K, Yamasue, H, Ohtomo, K (2012). Tract-specific analysis of white matter integrity disruption in schizophrenia. Psychiatry Research 201, 136–143.CrossRefGoogle ScholarPubMed
Meyer, J, Velasco, K, Gopi, M (2008). Tracking of oligodendrocyte remyelinated axons in spinal cords. International Conference on Stem Cell Engineering, American Institute of Chemical Engineers (AIChE) 23, 1–5.Google Scholar
Nasrallah, HA, McCalley-Whitters, M, Bigelow, LB, Rauscher, FP (1983). A histological study of the corpus callosum in chronic schizophrenia. Psychiatry Res 8, 251–260.CrossRefGoogle ScholarPubMed
Nolte, J (2002). Cerebral cortex. In The Human Brain. An Introduction to its Functional Anatomy (ed. Notle, J.), pp. 549–552. Mosby: Maryland Heights.Google Scholar
Ozalay, O, Calli, C, Kitis, O, Cagdas Eker, M, Donat Eker, O, Ozan, E, Coburn, K, Saffet Gonul, A (2013). The relationship between the anterior corpus callosum size and prefrontal cortex volume in drug-free depressed patients. Journal of Affective Disorders 146, 281–285.CrossRefGoogle ScholarPubMed
Park, HJ, Kim, JJ, Lee, SK, Seok, JH, Chun, J, Kim, DI, Lee, JD (2008). Corpus callosal connection mapping using cortical gray matter parcellation and DT-MRI. Human Brain Mapping 29, 503–516.CrossRefGoogle ScholarPubMed
Price, G, Bagary, MS, Cercignani, M, Altmann, DR, Ron, MA (2005). The corpus callosum in first episode schizophrenia: a diffusion tensor imaging study. Journal of Neurology, Neurosurgery and Psychiatry 76, 585–587.CrossRefGoogle ScholarPubMed
Riederer, F, Marti, M, Luechinger, R, Lanzenberger, R, von Meyenburg, J, Gantenbein, AR, Pirrotta, R, Gaul, C, Kollias, S, Sándor, PS (2012). Grey matter changes associated with medication-overuse headache: correlations with disease related disability and anxiety. World Journal of Biological Psychiatry 13, 517–525.CrossRefGoogle ScholarPubMed
Sackheim, HA, Greenberg, MS, Weiman, AL, Gur, RC, Hungerbuhler, JP, Geschwind, N (1982). Hemispheric asymmetry in the expression of positive and negative emotions: neurological evidence. Archives of Neurology 39, 210–218.CrossRefGoogle Scholar
Segal, D, Schmitz, C, Hof, PR (2009). Spatial distribution and density of oligodendrocytes in the cingulum bundle are unaltered in schizophrenia. Acta Neuropathologica 117, 385–394.CrossRefGoogle ScholarPubMed
Sexton, CE, McDermott, L, Kalu, UG, Herrmann, LL, Bradley, KM, Allan, CL, Le Masurier, M, Mackay, CE, Ebmeier, KP (2011). Exploring the pattern and neural correlates of neuropsychological impairment in late-life depression. Psychological Medicine 26, 1–8.Google Scholar
Sokolov, BP (2007). Oligodendroglial abnormalities in schizophrenia, mood disorders and substance abuse. Comorbidity, shared traits, or molecular phenocopies? International Journal of Neuropsychopharmacology 10, 547–555.CrossRefGoogle ScholarPubMed
Strigo, IA, Matthews, SC, Simmons, AN (2013). Decreased frontal regulation during pain anticipation in unmedicated subjects with major depressive disorder. Translational Psychiatry 3, e239.CrossRefGoogle ScholarPubMed
Uranova, N, Orlovskaya, D, Vikhreva, O, Zimina, I, Kolomeets, N, Vostrikov, V, Rachmanova, V (2001). Electron microscopy of oligodendroglia in severe mental illness. Brain Research Bulletin 55, 597–610.CrossRefGoogle ScholarPubMed
Uranova, NA, Vostrikov, VM, Orlovskaya, DD, Rachmanova, VI (2004). Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium. Schizophrenia Research 67, 269–275.CrossRefGoogle ScholarPubMed
Vostrikov, VM, Uranova, NA, Orlovskaya, DD (2007). Deficit of perineuronal oligodendrocytes in the prefrontal cortex in schizophrenia and mood disorders. Schizophrenia Research 94, 273–280.CrossRefGoogle ScholarPubMed
Wagner, G, Schultz, CC, Koch, K, Schachtzabel, C, Sauer, H, Schlösser, RG (2012). Prefrontal cortical thickness in depressed patients with high-risk for suicidal behavior. Journal of Psychiatric Research 46, 1449–1455.CrossRefGoogle ScholarPubMed
Waxman, SG, Kocsis, JD, Stys, PK (eds) (1995). The Axon: Structure, Function and Pathophysiology. Oxford University Press: Oxford.CrossRefGoogle Scholar
Williams, MR, Hampton, T, Pearce, RKB, Hirsch, SR, Ansorge, O, Thom, M, Maier, M (2012). Astrocyte decrease in the subgenual cingulate and callosal genu in schizophrenia. European Archives of Psychiatry and Clinical Neuroscience 263, 41–52.CrossRefGoogle ScholarPubMed
Williams, MR, Marsh, R, Jain, J, Macdonald, CD, Pearce, RKB, Hirsch, SR, Gentleman, S, Ansorge, O, Maier, M (2013). Neuropathological changes in the nucleus basalis in schizophrenia. European Archives of Psychiatry and Clinical Neuroscience 263, 485–495.CrossRefGoogle ScholarPubMed
Williams, MR, Pearce, RKB, Hirsch, SR, Ansorge, O, Thom, M, Maier, M (2006). Astrocytes abnormalities differentiate schizophrenia from affective disorders in post-mortem brain. Schizophrenia Research 81, Supplement, 72.Google Scholar
Xu, K, Jiang, W, Ren, L, Ouyang, X, Jiang, Y, Wu, F, Kong, L, Womer, F, Liu, Z, Blumberg, HP, Tang, Y, Wang, F (2012). Impaired interhemispheric connectivity in medication-naive patients with major depressive disorder. Journal of Psychiatry and Neuroscience 37, 110–132.Google Scholar